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Treating Massive Overdose

After evaluating this article, participants will be able to:
1. Incorporate strategies into clinical practice to appropriately identify massive overdoses
2. Improve patient safety by recognizing the complications associated with massive overdose of several common substances
3. More effectively recognize the toxic syndrome of massive overdoses

A 33-year-old female presented to the ED after ingesting the mercury contained in 2,500 thermometers (about 1000 mL). It took the patient one month to purchase the thermometers in drugstores and nine hours to extract the mercury by breaking the thermometers and filtering the mercury with gauze... What do you do? A case-driven report on the treatment of massive overdoses.

In recent years, a dramatic trend in overdoses has been observed in regards to the quantity and chronicity of drugs ingested for recreational and suicidal intent. Additionally, as patients become more habituated to specific drugs, their tolerance increases, requiring higher doses to achieve their desired effect. As a result, the commonly recognized therapeutic pharmacokinetic data of drugs may be overwhelmed and altered by toxicokinetics. Overdoses of common over-the-counter drugs, which generally result in mild toxicity, have been noted to result in profound CNS depression, respiratory failure, metabolic acidosis and multiple organ failure when taken in massive doses (Meehan - Thompson, 2010).

OTC Pain Reliever Medications

MASSIVE ASPIRIN
According to the recent Annual Toxic Exposures Survey from the American Association of Poison Control Centers’ National Poisoning and Exposure Database in 2008, there were more than 20,000 reported aspirin and non-aspirin, salicylate exposures, 64% of which required treatment in a health care facility. Of these exposures, 50% were reported as intentional overdoses, and 60 patients died (Herres 2009).

Salicylate toxicity continues to be encountered commonly in the emergency setting. The signs and symptoms of salicylate toxicity can often be subtle, (particularly with chronic toxicity) with erratic absorption and elimination kinetics, resulting in devastating physiologic effects of overdose (O’Malley 2007). Highlighting this phenomenon, recent fatality data noted in Poison Control Center records describe the following cases:

CASE ONE: A 50-year-old male ingested approximately 300 aspirin tablets and drank a bottle of mouthwash four hours prior to presenting to the ED. Upon presentation, he had progressive agitation requiring endotracheal intubation. Laboratory data revealed an initial ASA level of 62 mg/dl. Four hours later the level increased to 97 mg/dl. The patient was treated with activated charcoal, intravenous fluids, potassium, and bicarbonate therapy. Prior to hemodialysis, the patient developed dysrhythmias and torsades de pointes that led to cardiac arrest (Bronstein 2007 #586).

CASE TWO: A 45-year-old male took 400 tablets of aspirin (325mg) after a confrontation. He was found in his home five hours later “cold, blind, and unable to hear.” He suffered a seizure en route to the ED. On physical examination, the patient was described as combative, confused and febrile with a pulse of 155/min and respiratory rate of 36/min. The initial ASA level was 98 mg/dL. In the ED, he became unresponsive and suffered a cardiopulmonary arrest. Resuscitation was unsuccessful. He was pronounced dead within one hour of arrival (Bronstein 2008 #512).

CASE THREE: 45-year-old female presented to the ED four hours after ingesting 500 tablets of aspirin. She was decontaminated with oral activated charcoal. In the ICU, she was described as confused and combative. Her salicylate level at four hours was 80mg/dL; at 6 hours it increased to 109mg/dL. Whole bowel irrigation was instituted. The patient became unresponsive, was intubated, but expired before dialysis could be performed (Litovitz 2002 # 392).

MASSIVE IBUPROFEN
Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose in the vast majority of cases is uncommon. A recent case of massive ibuprofen ingestion reported a serum ibuprofen concentration much greater than previous fatal cases. The case was characterized by metabolic acidosis, coma and a state of high urine output. The patient survived with aggressive supportive care (Levine 2010).

Two fatalities resulting from massive ibuprofen ingestion were recently reported. Both overdoses were characterized by cardiovascular collapse, metabolic acidosis, hypothermia and multisystem organ failure despite the use of vasopressors and renal replacement therapy (Holubek 2007).

CASE ONE: A 17-year-old female was found in her bedroom by her family. She was unresponsive and surrounded by orange-colored vomitus. Next to her was a large bottle of ibuprofen (only one tab remained). The bottle advertised 1,000 tablets, 200mg each. The patient was comatose with a metabolic acidosis (pH 7.08) and hypothermia. The ibuprofen level was 352 mcg/mL. Despite intensive care and veno-hemofiltration, the patient expired.

CASE TWO: A 49-year-old male with bipolar disorder was discovered by his ex-girlfriend, comatose with shallow respirations in a fresh pool of vomitus. Next to him were two empty bottles of ibuprofen. The label advertised 600 tabs, 200mg each. Vitals noted a blood pressure of 60/45mmHg; pulse 115/min; and temperature of 89.3F. The serum pH was 6.71. Despite supportive care and hemodialysis, the man expired.

MASSIVE ACETAMINOPHEN
Acetaminophen (paracetamol) continues to be a leading cause of intentional and accidental poisoning resulting in profound hepatotoxicity. Widely available to the public over the counter, it is also found in many combination preparations for cough, cold, flu and decongestant therapy (Dear 2008). The US Food and Drug Administration (FDA), concerned about the incidence of acute liver failure due to acetaminophen overdose, has mandated new labeling on acetaminophen packaging. It is also considering (but has not enacted) reducing the maximum daily dose from 4 g, possibly to 3,250 mg, banning acetaminophen-narcotic combination products and changing the current maximum single dose of 1 g to prescription status, making 650 mg the highest recommended nonprescription dose (Schilling 2010). An acute ingestion of 200 g with a peak recorded serum acetaminophen level of 1,614 mg/L was recently reported (Wiegland 2010). The patient presented with early onset of coma, metabolic acidosis and hypotension in the absence of significant hepatic injury. In addition to N-acetylcysteine (NAC) therapy and CVV hemodialysis was performed to manage the acid-base disturbance

CASE ONE: According to Poison Control data, a 51-year-old woman presented to the ED after being found unresponsive and surrounded by vomit, stool and acetaminophen pills. The time of ingestion was unknown. In the ED, she was acidotic, hypothermic and required intubation. Her initial acetaminophen level was 1121mcg/mL with a pH of 6.9. Two 20-hour IV NAC regimens were completed but the patient expired on day four (Watson 2005 #288).

CASE TWO: 32-year-old female intentionally ingested 150 tabs of acetaminophen (500mg) in combo with diphehydramine (25mg). EMS found the patient naked and combative at home with vomitus in her hair, ears and on her face. Naloxone was administered with no effect. Diazepam and physostigmine was given and the mental status improved. The initial APAP level 540 mcg/mL. Oral N- acetylcysteine was initiated. Eighteen hours later, the patient demonstrated altered mental status, tachypnea, tachycardia and hypotension. Hemodialysis was instituted but the patient expired while waiting for a liver transplant (Watson 2003 #333).

Caffeine overdoses from weight loss regimens and energy drinks are on the rise, producing multiple symptoms, most of which are commonly associated with a marked increase in adrenergic tone. These can include hypertension, tachycardia, dysrhythmias and central nervous and skeletal muscle stimulation. Cases of massive caffeine ingestion with resultant neurotoxicity, seizures, cardiovascular collapse and death have also been reported (Kapur 2009).

Massive Heavy Metals

CASE ONE: A 40-year-old woman with a history of morbid obesity and gastric bypass ingested a large unknown amount of iron sulfate tablets in a suicide attempt. She presented to the ED with confusion, hematemesis and bloody diarrhea. She was hypotensive and tachycardic with an elevated glucose and white blood cell count. Gastric lavage demonstrated a fresh blood aspirate. Deferoxamine chelation was instituted after an iron level of 16,289 mcg/mL was measured. Emergent gastrectomy was contemplated, but the patient expired 30 hours post presentation (Watson 2006 #963).

CASE TWO: An 18-year-old man deliberately ingested termiticide containing a massive dose of arsenic trioxide. He was treated with the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA), which was replaced by dimercaprol therapy on days two through five. He required intensive support for multisystem organ failure, but recovered slowly with residual peripheral neuropathy (Kim 2009).

CASE THREE: A 33-year-old female presented to the ED after ingesting the mercury contained in 2,500 thermometers (about 1000 mL). It took the patient one month to purchase the thermometers in drugstores and nine hours to extract the mercury by breaking the thermometers and filtering the mercury with gauze. Ten minutes after drinking all the mercury, she vomited, producing 40 mL of gastric fluid mixed with mercury beads. Sixteen hours later she developed abdominal pain and sharp pains in her mouth. Abdominal films documented a large amount of mercury throughout the digestive tract. It took three weeks to completely expel the mercury. The patient was started on DMSA after a urine mercury level of 2,585/24 hour collection was documented. This was the largest oral mercury ingestion ever reported (Song 2007).

CONCLUSION

From a public health viewpoint, the recent massive overdose phenomena may be due to wider availability of prescription drugs and OTC medications (web availability and super stores dispensing up to 1,000 tabs per bottle). Another alternative explanation is an increased intent of self harm magnified by the rising prevalence of psychiatric disorders in our society with limited psychosocial resources for those in need.

This column represents a modified version of a section which appeared in the review article: Meehan T, Thompson T, Erickson T: New Overdoses: The Latest Trends in Poisoning. EM Reports, May 2010.